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Updated June 2026 · ClinicalTrials.gov

RECRUITINGPhase 1INTERVENTIONAL

GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

Phase I Study of GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies

GPC3 Targeted CAR-T Cell Therapy in Advanced GPC3 Expressing Solid Tumor Malignancies (NCT05003895) is a Phase 1 interventional studying Hepatocellular Carcinoma and Hepatocellular Cancer, sponsored by National Cancer Institute (NCI). RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

Background: A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer. Objective: To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe. Eligibility: Adults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy. Design: Participants will be screened with the following: Blood and urine tests Medical history Physical exam Heart function tests Review of their symptoms and their ability to perform their normal activities Tumor biopsy Imaging scan of the chest, abdomen, and pelvis Participants will have leukapheresis. They may have an IV (intravenous catheter, a small tube put into an arm vein) inserted into each arm or get a central line. Blood will be removed. A machine will separate the white blood cells from their blood. The rest of their blood will be returned to them. Participants will be admitted to the hospital for about 2 weeks. They will get the chemotherapy drugs fludarabine and cyclophosphamide by IV for 3 days. Then they will receive the modified white blood cells by IV. Participants will have frequent blood draws. They will give blood and tumor samples for research. Participants will have follow-up visits for the next 15 years. Then they will be contacted by email or phone for the rest of their life. If their disease does not get worse after 5 years, they will continue to be invited to do imaging studies every 6 months.

What Stage of Research Is This?

Phase 1 trials test a new treatment for the first time in humans, focusing on safety, dosing, and how the body processes the drug. For Hepatocellular Carcinoma, a Phase 1 study typically enrolls a small number of participants — often healthy volunteers or patients who have exhausted standard treatment options. Phase 1 results determine whether a treatment moves into larger Phase 2 efficacy studies.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 38 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

* Who May Qualify: - Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology - Participants must: - have progressed on at least 1 prior line of treatment OR --been intolerant of at least 1 prior line of treatment. - Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators. - Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy - Participants must have at least 1 measurable lesion by RECIST version 1.1 - Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation. - Age \>= 18 years. - Performance status (ECOG) 0-1 - Participants must have adequate organ and marrow function as defined below: ANC: \>= 1,000/mcL Platelets: \>= 75,000/mcL Hemoglobin: \>= 8 g/dL total bilirubin: If cirrhosis present: Part of Child Pugh requirement If no cirrhosis: bilirubin should be \<= 1.5 x ULN ALT or AST: \<= 5 x ULN. Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl) (A): \< 1.5x institution upper limit of normal OR \>= 50 mL/min/1.73 m\^2 for participant with creatinine levels, \>= 1.5 X institutional ULN ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. (A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language
* INCLUSION CRITERIA: * Histopathological confirmation of HCC or other solid tumor malignancy by the NCI Laboratory of Pathology * Participants must: * have progressed on at least 1 prior line of treatment OR --been intolerant of at least 1 prior line of treatment. * Participants must have at least 1 focus of disease that is amenable to mandatory tumor biopsy prior to study treatment initiation to determine tumor GPC3 expression and be willing to undergo this. Ideally, the biopsied lesion should not be one of the target measurable lesions, although this can be up to the discretion of the investigators. * Tumor must have GPC3 positivity of \>= 25% by immunohistochemistry on freshly collected biopsy * Participants must have at least 1 measurable lesion by RECIST version 1.1 * Participants must have a disease that is not amenable to potentially curative resection, ablation, or transplantation. * Age \>= 18 years. * Performance status (ECOG) 0-1 * Participants must have adequate organ and marrow function as defined below: ANC: \>= 1,000/mcL Platelets: \>= 75,000/mcL Hemoglobin: \>= 8 g/dL total bilirubin: If cirrhosis present: Part of Child Pugh requirement If no cirrhosis: bilirubin should be \<= 1.5 x ULN ALT or AST: \<= 5 x ULN. Creatinine OR Measured or calculated creatinine clearance (CrCl) (eGFR may also be used in place of CrCl) (A): \< 1.5x institution upper limit of normal OR \>= 50 mL/min/1.73 m\^2 for participant with creatinine levels, \>= 1.5 X institutional ULN ALT (SGPT)=alanine aminotransferase (serum glutamic pyruvic transaminase); AST (SGOT)=aspartate aminotransferase (serum glutamic oxaloacetic transaminase); GFR=glomerular filtration rate; ULN=upper limit of normal. (A)Creatinine clearance (CrCl) or eGFR should be calculated per institutional standard. * Normal cardiac ejection fraction (\>= 50% by echocardiogram) and no evidence of hemodynamically significant pericardial effusion as determined by an echocardiogram within 4 weeks before treatment initiation. * Room air oxygen saturation of 92% or greater. * Treatment-related toxicities must be resolved to \<= grade 1. * For participants with brain metastases: Participants with \<=3 (three or fewer) brain metastases that have been treated with surgery or stereotactic radiosurgery or other form of treatment are eligible. Lesions that have been treated with stereotactic radiosurgery must be clinically stable for one month before protocol treatment. * The study drugs are harmful to developing human fetus. For this reason, women of childbearing potential must agree to use highly effective contraception (hormonal, intrauterine device (IUD), abstinence, surgical sterilization) at the study entry and up to 12 months after the last dose of combined chemotherapy. Men must agree to use an effective method of contraception (barrier, surgical sterilization, abstinence) at the study entry and up to 4 months after the last dose of study drugs. We also recommend men with partners of childbearing potential ask their partners to be on highly effective birth control (hormonal, IUD, surgical sterilization). Men must not freeze or donate sperm within the same period. * HBV infected participants must be on antivirals and have HBV DNA \< 100IU/mL. HCV infected participants can be enrolled with close HCV RNA level monitoring. * Participants must be able to understand and be willing to sign a written informed consent. * For participants that do not have a legally authorized representative in place, one must be identified before study treatment starts Exclusion Criteria * Prior systemic therapy, an investigational therapy, radiation, and/or surgery within 2 weeks prior to treatment initiation. * Prior administration of anti-PD-1 or anti-PD-L1 antibodies or other agents that in the opinion of the PI can stimulate immune activity and interfere with an infusion of CAR-T cells within 8 weeks prior to treatment initiation. * Child-Pugh class B or C liver function * Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. Note: Participants with a history of abnormal pulmonary function tests but stable obstructive or restrictive pulmonary disease may be eligible per PI discretion. * Any form of primary immunodeficiency (e.g. severe combined immunodeficiency). * HIV-positive participants are excluded because HIV causes complicated immune deficiency and study treatment can pose more risks for these participants. * Participants receiving systemic steroids \>= 0.5 mg prednisone equivalent/kg/day. Steroid creams, ointments, and eye drops are allowed. Dose adjustment or discontinuation of medication must occur at least 24 hours prior to conditioning chemotherapy. Use of CART cell therapy in autoimmune diseases has the potential to be associated with serious safety risk. Given that this is an evolving area of research, caution should be exercised and any decision to include participants with autoimmune diseases should be made on a case-bycase basis. * History of severe immediate hypersensitivity reaction to cyclophosphamide or fludarabine. * Hospitalization within 7 days prior to treatment initiation. * Pregnant women are excluded from this study because study therapy can cause fetal harm. Because there is a potential risk for adverse events in nursing infants secondary to treatment of the mother with study therapy, breastfeeding should be discontinued if the mother is treated with study drugs. * Participants who received live or attenuated vaccine or virus-based vaccine within 30 days before initiation of study therapy * Participants with a history of seizure disorder * Participants with an expected life expectancy of less than 3 months before initiation of study therapy.

Treatments Being Tested

DRUG

Cyclophosphamide

Daily x 3 doses on Day -3, -2, -1 300 mg/m2 IV infusion (200 mg/m\^2 in Dose Level -1)

BIOLOGICAL

CAR-T cell

Single infusion on Day 0

DRUG

Fludarabine

Daily x 2 doses on Day -2 and -1 30 mg/m\^2 IV infusion administered following cyclophosphamide

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

National Institutes of Health Clinical Center
Bethesda, Maryland, United States

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05003895), the sponsor (National Cancer Institute (NCI)), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05003895 clinical trial studying?

Background: A new cancer treatment takes a person s own T cells, modifies them in a laboratory so they can better fight cancer cells, and then gives them back to the person. Researchers want to see if this treatment can help people with a certain types of cancer. Objective: To see if a personalized immune treatment, anti-GPC3 CAR-T cells, is safe. Eligibility: Adults aged 18 years and older who have Glypican-3 (GPC3) positive solid tumor malignancy. Design: Participants will be screened with the following: Blood and urine tests Medical history Physical exam Heart function tests Rev… The full protocol is registered on ClinicalTrials.gov and includes the primary outcome measures, eligibility criteria, and study endpoints.

Who can participate in NCT05003895?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05003895?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05003895. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05003895. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-06-26 · Data from ClinicalTrials.gov.